1. Field of Invention
The present invention relates to methods of producing composite structures in parallel and to composite structures made by the methods.
2. Discussion of Related Art
One of the primary goals of synthetic colloidal chemistry is to create new kinds of particles that have a wide variety of shapes and functionalities and overall sizes in the range from a few microns to a few nanometers. The dominant approach taken by many groups worldwide is through bottom-up synthesis, including “self-assembly”1 of atomic, molecular, and supramolecular components. Self-assembled structures can be simple, such as spheres2, disks3, platelets4, and cubes5. They can also be more complex, such as tetrapods6, clusters7, liposome-microtubule complexes8, and colloidosomes9. Random thermal forces cause colloidal particles to diffuse rapidly in a liquid regardless of their structures; this Brownian motion can overcome gravity and keep the particles dispersed homogenously over long times10. Despite the increasing sophistication of self-assembly approaches, including multi-step procedures, that have produced a rich variety of new structures11, no universal recipe exists for creating monodisperse colloids that have arbitrarily prescribed shapes and sizes using bottom-up approaches.
One of the current inventors has demonstrated that high-throughput automated stepper lithography can be used to generate bulk dispersions of an enormous range of desirable particle shapes having exquisite fidelity in the colloidal length scale range (See PCT/US2007/018365 filed Aug. 17, 2007 assigned to the same assignee as the current application, the entire contents of which are incorporated herein by reference). These stepper-produced lithographic particles, or “LithoParticles”, can be designed to have a virtually limitless diversity of crisp monodisperse shapes that have structures well below 10 microns in lateral dimensions. By contrast to most micro-electromechanical systems (MEMS)12 applications, in which the desired structures remain attached to the wafer's surface, in our application, the LithoParticle structures, created by UV-exposure and development, are completely liberated from the wafer's surface by total lift-off into a liquid. The wafers merely serve as re-useable flat substrates for making the particles. As a demonstration of the power of this approach, we have designed and fabricated “colloidal alphabet soup”: a dispersion of microscale polymer LithoParticles representing all twenty-six letters of the English alphabet in a viscous liquid. Moreover, we demonstrated control over the color and internal composition of the LithoParticle letters by incorporating red, green, and blue fluorescent dyes into them. By successively coating more than one layer of resist and exposing using different masks, we have built up complex three-dimensional LithoParticles that are not limited to simple slab-like shapes and can be used to create complex layered internal compositions. These advances represent major breakthroughs in designing model colloids over top-down efforts in micromachining13-15 and imprintation16 work to which we have contributed.
We can produce high-fidelity polymeric LithoParticles by the following versatile method. Polished wafers are spin-coated first with a sacrificial layer of water-soluble polymer and subsequently with a layer of UV-sensitive photoresist [FIG. 1(a)]. The thickness of the resist layer can be controlled from about 100 nm to many microns with excellent uniformity over the entire wafer's surface12. A high-throughput, robotically-automated, ultraviolet (UV), lithographic projection exposure system, or “stepper”, is used to rapidly expose the photoresist at sub-micron feature-sizes12. The spin-coated wafers are exposed with the mask patterns of letters or other shapes on a photomask at 5× reduction using an Ultratech i-line stepper. This exposure causes cross-linking of the polymer resist [FIG. 1(b)]. An organic developer removes the unexposed resist without dissolving the sacrificial layer; as a result, the sacrificial layer is covered with a dense array of particles [FIG. 1(c)]. By dissolving the water-soluble sacrificial layer, the particles are lifted completely off of the surface into aqueous solution [FIG. 1(d)]. Surface charges on the particles inhibit aggregation for pH>8. Once in solution, methods of surface chemistry and solvent exchange can be used to further stabilize the particles and change the liquid from aqueous to non-aqueous2.
The details of our synthetic procedure are as follows. LithoParticles are produced by successively spin-coating two uniform layers onto five-inch polished diameter silicon wafers. Water-soluble Omnicoat (Microchem) is initially spun onto each wafer at 3,000 rpm to produce a sacrificial layer of 0.3 μm. Next, SU-8 2001 epoxy resist in cyclopentanone is laden with red, green, and blue fluorescent dyes by adding 0.0015 g each of either Nile Red, NBD-X, or 2,6-ANS (Invitrogen) to 15 mL of SU-8 and mixing thoroughly. Each of the SU-8 solutions is then spin-coated over the sacrificial Omnicoat layers at 3,000 rpm, producing a resist layer thickness of 1.0 μm. By contrast to some photoresists, crosslinked SU-8 exhibits little optical absorption in the visible spectrum and has good chemical resistance. The density of the SU-8 after baking and removing the solvent is 1.24 g/cm3. A reticle-mask (Toppan) that contains all 26 letter of the English alphabet in high density (area fraction of approximately 50%) is created by electron beam lithography (MEBES) using a layout designed in L-Edit software (Tanner EDA). The lateral dimensions of a letter on the reticle are about 35 μm×20 μm. The wafers are then exposed to 365 nm light, using an Ultratech 2145 i-line stepper (5× reduction, 0.35 micron feature size, wavelength 365 nm) with an automated wafer handling system capable of 60 wafers/hour, at a power of 233 mJ/cm2 (optimized for feature fidelity). The lateral dimensions of the printed letters after 5× reduction by the stepper are 7 μm×4 μm with only a 1 μm pen-width. We have obtained sub-micron pen-widths for other shapes using a different mask. The wafers are developed first by organic SU-8 developer using mild agitation, and then are lifted off of the wafer surfaces into aqueous solution using water-based Omnicoat developer. After lift-off, the particles are stable against aggregation in basic solutions but can begin to aggregate if the pH is changed to be acidic. Surface functionalization and surface modification chemistry, if desired, is performed on the particle surfaces at this stage, typically immediately after lift-off before any irreversible aggregation or clumping occurs. After producing three separate bottles of monodisperse red, green, and blue fluorescent microscale letters, we mix them together to form multi-colored fluorescent colloidal alphabet soup of LithoParticles in water suitable for multi-line excitation and detection using confocal microscopy.
Probing the thermally-driven dynamics of systems of many interacting particles that have interesting and varied non-spherical shapes in three-dimensions may help unlock the mysteries of self-assembly. Since fast 3-d confocal microscopy is an excellent tool for studying colloidal model systems, we have developed dispersions of colloidal LithoParticles that are compatible with confocal microscopy by incorporating red, green, and blue fluorescent dyes into the resist prior to spin-coating. We have optimized the concentrations of the dyes to provide bright fluorescence, yet these concentrations are low enough that we can still adjust the stepper's exposure to provide the necessary cross-linking that maintains the mechanical integrity of the particles. We have created separate aqueous solutions of red, green, and blue fluorescent microletters; after combining these solutions, we have used multi-wavelength excitation and detection laser scanning confocal microscopy (TCS SP2 AOBS laser-scanning microscope: Leica) with a 63× oil-immersion objective (NA 1.40) to obtain an image section of red, green, and blue colloidal alphabet soup [FIG. 2(a)]. After thresholding and cross-filtering the red, green, and blue channels, a composite image is created. Although some concepts of shape-dependent assembly of non-spherical disk-shaped particles driven by depletion attractions have been previously introduced to make columnar aggregates of microscale disks3, a non-obvious application of depletion attractions with LithoParticles can be used to create columnar assemblies of crosses in which the arms of the crosses are highly aligned, interdigitated and angular offset aggregation of crosses, columnar tubes comprised of square donuts, lock-and-key aggregation caused by the insertions of an arm of a cross into the hole of a donut, and the formation of a cup by causing a donut to aggregate face-to-face with a cross [FIGS. 2(b)-(e)]. In all these examples, the small spheres used as a depletion agent, which create the depletion attraction between the larger objects, are nanoemulsion droplets17 having an average radius of 57±5 nm at a droplet volume fraction of 0.1.
Due to the high resolution of the stepper, the control over the shapes of the letters is exquisite. The effective width of the pen that has written the letters is about 1.0 μm, as we intended. Scanning electron microscope (SEM) images of the letters [FIG. 3(a)] reveal a striking crispness and high degree of uniformity: the polydispersities in lengths and in thicknesses of the letters are less than 10%. These SEM images are obtained by drying particles on a Ni/Cu tape (Ted Pella Inc.) and sputtering 5 nm of gold using a Hummer 6.2 Sputterer (Anatech Ltd.) to reduce charging. Images are acquired using a field emission JEOL JSM-6700F SEM at a working distance of 8 mm and at 10 kV and 10 μA. Jamming18 and interlocking of the deposited particles is evident. Indeed, the interlocking of particles that have “arms” and “hooks” in a disordered structure is actually an unusual non-equilibrium jammed state that can support tension; simpler particle shapes, such as spheres19 and ellipsoids20, which can only support compression, repulsively jam but do not interlock. In addition to letters, we have designed a variety of smaller particle shapes based on a single layer: square donuts (toroidal particles with a hole), square crosses (particles with four arms in the same plane), triangular prisms, and pentagonal prisms [see FIGS. 3(b)-(e)]. The Brownian motion of these particles in solution is very noticeable. By adapting stabilization and solvent exchange procedures21, one can match both the refractive index and the density of these particles in organic solvents.
The robotic automation of the stepper's exposure can be used to rapidly mass-produce bulk dispersions of LithoParticles. Five-inch wafers, exposed at one wafer per minute, yield roughly a quarter of a billion particles per minute, permitting the production of bulk dispersions. This production rate far surpasses that of other top-down methods, such as continuous-flow lithography22, which has reported rates of a hundred particles per second. The stepper provides massively parallel high throughput while maintaining superior alignment and exposure fidelity arising from a mechanically stable platform. By incorporating all of the equipment for making LithoParticles into a robotically automated track system, a continuous rate of 108 particles per minute can be achieved.
Beyond incorporating fluorescent dyes into single-layer particles, we have achieved a high level of control over the internal composition of the particles and have achieved complex multi-layer structures. For instance, we have produced both fluorescent and magnetically-responsive LithoParticles by incorporating a variety of organic dyes and organically-coated nanoparticles, such as iron-oxide, into the photoresist layer prior to exposure and crosslinking. In addition, we have created complex 3-d multilayer LithoParticles by coating and exposing layers in succession using a set of reticles that represent the cross-sections of desired 3-d shape at different heights. As a simple example, we show hybrid bilayer Janus LithoParticles that have been created by exposing a lower resist layer laden with blue fluorescent dye with the square cross pattern, and then coating a second layer of resist containing red dye, aligning, and exposing with the triangular pattern [FIG. 4]. A microscopic dark field alignment system (μ-DFAS) is used by a piezoelectric feedback system to align the previously exposed wafer with the new reticle. Holographic laser tweezers can also be used to create complex 3-d colloidal structures23, yet the throughput and edge fidelity of the stepper-based method is much higher. Using our approach, deep-UV steppers with sub-100 nm feature sizes, could produce colloidal particles having dimensions smaller than 1 μm×0.6 μm×0.1 μm.
The high-throughput production of customizable colloidal LithoParticles by automated stepper technology may open doors for many new research directions. One very exciting area is to use confocal microscopy to study the process of thermally-driven self-assembly of differently shaped components that have controlled interactions24. In essence, we can use the power of top-down lithography to generate model dispersions of monodisperse colloidal LithoParticles, for example, that can enable us to study and understand the science of bottom-up self-assembly. This problem lies at the heart of understanding structure-function relationships in molecular biology, for example. In order for thermally driven self-assembly to occur in a reasonable time, Brownian motion of the components should be significant. Larger particles generated using other lithographic methods are not truly colloidal and may not be useful to explore self-assembly, because the extremely slow diffusion of larger structures make self-assembly studies impractical. By contrast, our single-layer and multi-layer fluorescent LithoParticles are small enough that dynamics, such as phase transitions and self-assembly, can be explored in three dimensions using fast confocal microscopy25. Indeed, deep-UV steppers could produce sub-micron LithoParticles that would diffuse and self-assemble even more rapidly.
In addition to providing model systems of complex shapes, LithoParticles can be used in a wide range of other applications. In cell biology, LithoParticles could serve as novel fluorescent probes that may be customized and adapted to study dynamic changes of microstructures inside cells. LithoParticles that have tailored surface functionalization, such as charge groups26 or DNA27, could provide new and interesting possibilities for creating artificial interacting architectures24. Single component or multicomponent model systems of LithoParticles can be used to explore the equilibrium phase behavior and phase transitions of mixtures of non-spherical shapes28, providing a better understanding of the fundamental science of liquid crystals. LithoParticles that have arms, whether straight or curved, can jam and interlock to form unique colloidal glasses29. By manipulating LithoParticles with laser tweezers30, one may be able to mark cells with a desired shape or letter. Combining top-down LithoParticles with bottom-up synthetic approaches, such as those used to form colloidosomes9 and dense clusters7, would offer an even greater range of interesting and potentially useful morphologies.
The advent of multi-layer monodisperse LithoParticles, including Janus LithoParticles, which have feature sizes around one micron or less, represents an important advance in lithographic colloidal dispersions. Colloidal LithoParticles exhibit significant Brownian motion and provide building blocks suitable for use in thermodynamic self-assembly driven by selective interactions, such as depletion attractions, and thermal diffusion. We have demonstrated controlled production of toroidal particles and shape-specific lock-and-key assembly. Moreover, single-layer and multi-layer particles can be made from a great range of materials, including organic, inorganic, and metallic materials.